Publications by authors named "Mark Tuthill"

Purpose: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile.

Methods: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg).

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Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality.

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Context.—: Intraoperative diagnosis by frozen section is a mainstay of surgical pathology practice, providing immediate feedback to the surgical team. Despite good accuracy with modern methods, access to intraoperative surgical pathology with an appropriate turnaround time (TAT) has been a limiting factor for small or remote surgical centers, with negative impacts on cost and patient care.

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Background: Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience.

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Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer.

Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer.

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Purpose: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.

Methods: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021.

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Background: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level.

Methods: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021.

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Background: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory.

Methods: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved.

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Article Synopsis
  • The study investigates immune checkpoint inhibitor (ICI)-colitis to understand its causes and similarities to idiopathic ulcerative colitis, aiming to find new treatment targets.
  • Key findings reveal that activated CD8 T cells are predominant in ICI-colitis, and their activation is linked to the severity of the condition, differing from the patterns seen in ulcerative colitis.
  • The research highlights that targeting these activated CD8 T cells with the JAK inhibitor tofacitinib shows promise as a treatment for ICI-colitis.
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Background: Gross imaging of surgical specimens is paramount for the accurate gross examination and diagnosis of disease. Optimized imaging workflow can facilitate consistently high-quality gross photographs, especially in high-volume, metropolitan hospitals such as ours. Most commercial medical gross imaging technology provides ergonomically well-designed hardware, remotely operated cameras, intuitive software interfaces, and automation of workflow.

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In 2018, there were 400,000 new cases of renal cell carcinoma (RCC) globally, with 175,000 deaths attributable to the disease. Three quarters of patients have potentially curable localised disease at diagnosis; however, recurrence rates are as high as 40% following surgery. There are currently no adjuvant therapies in routine clinical use which reliably improve outcomes.

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Article Synopsis
  • The study investigates the effectiveness of ctDNA testing in advanced breast cancer, aimed at avoiding repeat biopsies and helping to select patients for targeted therapies based on their genetic mutations.
  • Conducted across 18 UK hospitals, it involved women with advanced breast cancer who had undergone prior treatments, and assessed responses to various mutation-specific treatments aligned with their ctDNA profiles.
  • The trial is ongoing, with recruitment completed and primary endpoints focused on measuring response rates, and is registered under several clinical trial databases.
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Background: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.

Methods: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018.

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Background: Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.

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To achieve effective laboratory automation, analytical capabilities must be developed to support data analysis. This allows for effective development and deployment of decision support strategies within the automated laboratory. Practically, these take the form of dashboards, static and real time; workflow processes, such as autoverification; reflex protocols; and testing cascades, which reduce errors of omission and commission.

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Introduction: A whole slide image (WSI) is typically comprised of a macro image (low-power snapshot of the entire glass slide) and stacked tiles in a pyramid structure (with the lowest resolution thumbnail at the top). The macro image shows the label and all pieces of tissue on the slide. Many whole slide scanner vendors do not readily show the macro overview to pathologists.

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Aim: This narrative review describes current guidelines for treating NMIBC, provides an overview of the principle behind immune checkpoint inhibition, and summarizes current evidence for checkpoint inhibitors in urothelial malignancy. Further, we discuss potential strategies for immune checkpoint inhibition in the management of NMIBC.

Background: Adjuvant intravesical BCG immunotherapy has been the mainstay of treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) for decades but is associated with both a significant side effect profile and failure rate.

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Background: The alumni of today's Pathology Informatics and Clinical Informatics fellowships fill diverse roles in academia, large health systems, and industry. The evolving training tracks and curriculum of Pathology Informatics fellowships have been well documented. However, less attention has been given to the posttraining experiences of graduates from informatics training programs.

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Background: Stage 1 seminoma is frequently cured by radical orchiectomy; however, the management strategies after this diagnosis vary in terms of the use of adjuvant treatment and the nature of the follow-up protocols. We analyzed stage 1 seminomas treated in the Thames Valley Cancer Network for outcomes to determine whether any factors are predictive of recurrence. We also studied relapses to determine the optimal follow-up schedule and protocol.

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Whole-genome sequencing (WGS) has transformed the understanding of the genetic drivers of cancer and is increasingly being used in cancer medicine to identify personalized therapies. Here we describe a case in which the application of WGS identified a tumoral deletion in a patient with aggressive dedifferentiated prostate cancer that was repeat-biopsied after disease progression. This would not have been detected by standard BRCA testing, and it led to additional treatment with a maintenance poly ADP ribose polymerase (PARP) inhibitor following platinum-based chemotherapy.

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Objective: To update the demographic data, treatment details and outcomes for GTN patients with brain metastases managed with the modern treatment protocols at the UK centre for gestational trophoblast neoplasia at Charing Cross Hospital in London.

Methods: The hospital database and pharmacy records were reviewed to identify GTN patients treated with brain metastases. Data was assembled on the specific GTN diagnosis, staging, prognostic scores, chemotherapy regimens, additional interventions and outcomes.

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